Biodegradable polymers have been widely used to construct medical devices, particularly implantable medical devices. Compared to the conventional metallic material, biodegradable polymers offer many advantages. First, biodegradable polymers are conformable and flexible, thereby causing less stress to the biological tissues. Second, medical implants made from biodegradable polymers do not require a second surgical intervention for removal. Third, the biodegradable polymers may be used to enhance the therapeutic effect of a medical implant. For example, a fractured bone that has been fixated with a rigid metal implant has a tendency for refracture upon removal of the metal implant because the stress is borne by the rigid metal, so the bone has not been able to carry sufficient load during the healing process. In contrast, a biodegradable polymer can be tuned to degrade at a certain rate so that an implant prepared therefrom will slowly transfer load to the healing bone. In addition, biodegradable polymers are useful in drug delivery systems. For example, a therapeutic agent can be admixed with a biodegradable polymer to form a polymer matrix. The release rate of the therapeutic agent in such a polymer matrix can be controlled by adjusting the degradation rate of the biodegradable polymer.
Biodegradable polymers can be either natural or synthetic. In general, synthetic polymers offer greater advantages than natural materials since the synthetic polymers can be tailored to give the desirable properties according to their intended use. Synthetic polymers also offer better consistency and uniformity than natural polymers do. Furthermore, unlike natural materials, synthetic polymers cause little immunogenic responses after implantation. Common synthetic biodegradable polymers include polyglycolide, polylactide, poly(lactide-co-glycolide), polydioxanone, polycaprolactone, poly(hydroxyl butyrate), poly(trimethylene carbonate), polyphosphoester, polyphosphazene, and other poly(esteramide).
However, most biodegradable polymers are not radio-opaque. Consequently, medical devices made from those biodegradable polymers cannot be visualized by means of radiographic imaging. The ability to see the radiographic image of a medical device being used in, or implanted within, the body is very important since radiographic imaging provides a physician the ability to monitor and adjust the medical device during operation. For some medical implant applications, X-ray visibility is mandatory.
To achieve desirable radio-opacity in polymeric materials, one conventional method utilizes inorganic radiographic contrasting agents, such as barium sulfate, zirconium dioxide, or bismuth halides as additives or fillers in the polymeric material to form a radio-opaque polymeric matrix. However, these inorganic agents do not mix well with polymeric materials and may cause phase separation in the radio-opaque polymeric matrix. The phase separation problem is further aggravated since high concentrations (around 10%, and often times 20-30% by weight) of these inorganic radiographic contrasting agents are routinely used to obtain the required radio-opacity. The incompatibility between the polymeric and inorganic phases compromises the physicomechanical properties of the polymer matrix. Another disadvantage of using inorganic radiographic contrasting agents is the toxicity to tissues caused by the leach-out of these inorganic agents.
An alternative approach to introduce radio-opacity into polymeric materials is to synthesize polymers having covalently bound bromine or iodine atoms that may produce a radiographic contrasting effect (See U.S. Pat. No. 6,426,145). One radio-opaque composition of the prior art comprises a polymer having a non-leachable radio-opaque moiety covalently attached to the polymer (See U.S. Pat. No. 6,599,448), wherein the non-leachable radio-opaque moiety includes halogen substituted aromatic groups. The prior art has also disclosed a radio-opaque polymeric material comprising a diphenol-based monomer unit substituted with at least one bromine or iodine atom (See U.S. Pat. No. 6,852,308). However, preparations of these prior art radio-opaque polymers require synthesis of radiographic contrasting monomer units, which may increase the technical complexity and production cost.
Thus, there remains a need for a non-leachable radiographic contrasting agent that can provide enhanced contrasting intensity and a radio-opaque polymeric material that can be readily prepared from such a non-leachable radiographic contrasting agent and common biodegradable monomers.